Direct use of weighted Quantum Chemical Energy for ligands in BUSTER refinement:

QM helper applications

As described in the Introduction to the method page BUSTER uses helper executable invocations to evaluate the potential energy and its gradients for any given ligand position. This page provide the source code and technical details of the helpers.

By default BUSTER calls the helper with a method 'AUTO' the helper then selects the semi empirical model to be used according to the atomic numbers of the atoms supplied. The first method that treats all element types in the supplied molecule is selected from the list:

GAMESS helper script

GAMESS is an excellent quantum chemistry program maintained by the Gordon research group at Iowa State University. "A site license for GAMESS is available at no cost to both academic and industrial users".

Although semi empirical quantum methods are reasonably accurate, ab initio and DFT methods can be more so (but are much more computationally expensive).

Please refer to the GAMESS homepage for details of how get a license, download and setup GAMESS.

Please make sure the GAMESS script rungms works properly before trying to use it with BUSTER. In case it helps our localized version of the GAMESS rungms script can be downloaded here: rungms.

The default (AUTO) method is HF/3-21G(d)_pcm. This is a small basis set ab initio method and PCM water is used to reduce the electrostatics. This method has yielded good results in initial tests, see 2qxs tutorial example.

For testing to get the script working it is sensible to use -qm_method AM1 for speed.

OpenEye helper programs

The MMFF94 force field helper can be used through the -forcefield option and provides new capabilities, see AutobusterLigandForcefield No additional scripts are required.

The first version of the helpers v 2.3.0.4 truncated coordinates to a limited number of figures on read. This will be fixed on the next release. It has a little effect on practical applications.

Using autoBUSTER refine macro feature to make using QM helper easier for users

The command line options for using a helper that invokes 3rd party QM software are long and not easy to remember!

the autoBUSTER user-created macro feature is designed to help with exactly this kind of thing. It is explained in detail in the documentation online or in you local documentation that can be located using refine -h

for example we will create macros to use the GAMESS helper script as installed at Global Phasing with the what we find to be the most useful QM representations.

first make sure that the QM software and helper are correctly installed and working, for instance by running the test.

Create a directory to contain the macros. This directory should be separate from the BUSTER distribution. Here we use the directory /home/osmart/qmmacros

In this directory use your favorite editor to create a macro like:

vi gamessHF321.macro

file contents

# use GAMESS qm helper using HF/3-21(d) with pcm water
# you will algamessHF321.macroso need to specify residue like "-qm LIG"
# or if charged "-qm XXX+1"
+BusterExtraArgs="-qm_method HF/3-21G(d)_pcm -qm_helper /home/osmart/autobuster/gelly/helpers/gelly_qm_helper_gamess.pl"

clearly your macro will need to be adapted for your site and QM helper!

In practice it would be sensible to create a number of macros with different QM options and/or helpers.

To use the macros with refine set the environment variable autoBUSTER_MacroDirs to the directory name containing the macros. Exactly how you do this depends on what shell you use. For tcsh type or include in ~/.cshrc or ~/.login:

setenv autoBUSTER_MacroDirs /home/osmart/qmmacros

for bash shell

export autoBUSTER_MacroDirs=/home/osmart/qmmacros

Once you have done this, the macro(s) should be usable in refine. A good check is to list the available macros by refine -M list:

refine -M list
---------------------------------------------------------------------------
Macro name Description
---------------------------------------------------------------------------
edited
gamessHF321 : use GAMESS qm helper using HF/3-21(d) with pcm water
you will also need to specify residue like "-qm LIG"
or if charged "-qm XXX+1"
edited

Then to use the macro issue its name after -M, for example to use the GAMESS HF321 macro for a neutral ligand with 3 letter code INH use the option

refine -p in.pdb -m in.mtz -d 01 \
-qm LIG -M gamessHF321 > 01.log &

Methanol gradients test for helper scripts

To check that a helper script is working properly it is useful to runs check on a small molecule. In particular it is important for the helper to provide the correct gradient vector (minus the force). This can be checked by comparing the vector with numerical derivatives, calculated by the central differences method.